Ketamine, a dissociative anesthetic with therapeutic and recreational applications, poses significant toxicological risks, particularly when misused. This case report describes a 24-year-old male who presented to the emergency department with altered mental status, agitation, visual hallucinations, hyperthermia (103°F), and respiratory distress, including stridor and intermittent laryngospasm, following suspected recreational drug use. Clinical findings such as dilated pupils, horizontal nystagmus, rhabdomyolysis (elevated creatine kinase), leukocytosis, hypoglycemia, and mild phencyclidine (PCP) positivity suggested ketamine toxicity as the primary diagnosis. The patient required rapid-sequence intubation for airway protection, along with intravenous benzodiazepines for agitation and sympathetic overactivity, and aggressive intravenous (IV) fluid resuscitation for rhabdomyolysis. Hyperthermia was addressed with external and internal cooling methods. Sodium bicarbonate therapy was initiated to alkalinize urine due to creatine kinase (CK) elevation, and preparations for managing potential hyperkalemia were made. Imaging revealed bladder and ureteric wall thickening, raising suspicion of ketamine-induced cystopathy and prompting urologic evaluation. Given the severity of symptoms, the patient was admitted to the intensive care unit (ICU) for further monitoring and management. Activated charcoal was withheld due to timing and airway protection. This case emphasizes the importance of early recognition and comprehensive supportive care in ketamine toxicity, particularly when complicated by airway compromise, rhabdomyolysis, and hyperthermia, and underscores the role of psychiatric evaluation in suspected substance misuse.

Ketamine toxicity, Hyperthermia, Rhabdomyolysis, Hallucination, Hyperkalemia.

Ketamine is a dissociative anesthetic originally synthesized in 1962 as a derivative of PCP. Though structurally related to PCP, ketamine is significantly less potent and associated with fewer dysphoric and hallucinogenic side effects. It received FDA approval. (FDA) approval in 1970 and gained popularity as a battlefield anesthetic during the Vietnam War. [1]

Ketamine’s dissociative and euphoric properties have contributed to its misuse as a recreational drug. At low doses, it produces feelings of detachment and euphoria (“k-land”), while higher doses can induce immobilization and hallucinations (“k-hole”). It is sold illicitly under various names such as “Special K,” “Vitamin K,” and “Jet”.[2] Ketamine toxicity encompasses a wide range of clinical manifestations that affect neurological, psychiatric, cardiovascular, gastrointestinal, and urogenital systems. The symptoms and severity vary depending on dose, route of administration, and whether use was therapeutic or recreational. Chronic use is particularly associated with urinary tract complications like ulcerative cystitis.[3]

Globally, ketamine misuse is present in at least 58 countries, though it remains less prevalent than other illicit substances. The United Nations Office on Drugs and Crime noted that PCP-type drugs, including ketamine, constituted only about 1% of all new psychoactive substances as of 2014.[4] In the United States, where ketamine has been classified as a Schedule III controlled substance since 1999, misuse remains relatively rare compared to opioids or cannabis. Ketamine-related emergency department (ED) visits were low, accounting for just 0.033% in 2005 and rising to 0.12% in 2011, with the majority involving co-use with alcohol or other stimulants. Youth surveys have shown a decline in ketamine use among adolescents and college students since the early 2000s. [1]

In contrast, ketamine misuse is more widespread in parts of Southeast Asia. In Hong Kong, where it has been scheduled as a controlled substance since 2000, ketamine became the most abused drug in the early 2000s.[5] Toxicity may arise from both medical and non-medical use. Therapeutically, toxicity can occur through parenteral or intranasal administration, whereas recreational misuse commonly involves insufflation, injection, oral ingestion, or smoking. Illicit ketamine is often adulterated, compounding its toxicity profile.[6]

Ketamine primarily acts as a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, disrupting excitatory glutamatergic transmission. It also interacts with numerous other receptors and ion channels: it inhibits muscarinic and nicotinic acetylcholine receptors, blocks sodium and potassium channels, and stimulates dopaminergic, serotonergic, and adrenergic systems. These actions underlie its dissociative, analgesic, and sympathomimetic effects. While ketamine increases blood pressure and heart rate via sympathetic activation, it can cause hypotension in catecholamine-depleted patients. Its analgesic effects are not reversed by opioid antagonists like naloxone, despite some activity at opioid receptors.[7]

A 24-year-old male presented to the emergency department with altered mental status, severe agitation, visual hallucinations, and hyperthermia after attending a social event where the use of party drugs was suspected. On arrival, his vital signs showed a heart rate of 120 bpm, blood pressure of 150/90 mmHg, and a body temperature of 103°F. A fingerstick glucose test revealed hypoglycemia with a level of 3.96 mmol/L.

Physical examination revealed signs of respiratory distress, including stridor and episodes of intermittent laryngospasm, suggesting upper airway obstruction. Neurological findings included dilated pupils, horizontal nystagmus, peripheral cyanosis, and myoclonic jerks. Laboratory investigations indicated leukocytosis, elevated blood urea nitrogen (BUN), creatinine, and creatine kinase levels. A mildly elevated serum phencyclidine (PCP) level was detected, but no evidence of co-ingested substances was found. Urinalysis was notable for increased myoglobin, suggesting rhabdomyolysis. Electrocardiography (ECG) demonstrated a normal sinus rhythm. Imaging with a head computed tomography (CT) and cerebrospinal fluid (CSF) analysis ruled out intracranial pathology or infection.

Based on the clinical presentation and investigative findings, suspected ketamine toxicity leading to consideration, with complications including hyperthermia, rhabdomyolysis, and upper airway compromise.

The patient was treated with rapid-sequence intubation (RSI) due to signs of laryngospasm and impending airway compromise, with IV lidocaine (1.5 mg/kg) administered pre-intubation to reduce reflex spasms. Paralysis was achieved using succinylcholine or rocuronium, though these agents were used cautiously given the risk of hyperkalemia from concurrent rhabdomyolysis. For milder respiratory symptoms, humidified oxygen was provided. For cardiovascular stabilization, the patient received IV benzodiazepines (lorazepam 2-4 mg or diazepam 5-10 mg) to control hypertension and tachycardia, while avoiding beta-blockers to prevent unopposed alpha stimulation. Aggressive IV fluid resuscitation (1- 2L normal saline /lactated Ringer’s (NS/LR) bolus followed by 200-500 mL/hr maintenance) was initiated to maintain urine output of 1-2 mL/kg/hr for rhabdomyolysis management.

Critical hyperthermia (103°F) was treated with ice packs to neck/axilla/groin, cooling blankets, evaporative cooling, and cold IV fluids (4°C normal saline, 500-1000 mL), with a goal of reducing temperature below 38.5°C within 30-60 minutes. Dantrolene was kept available for potential malignant hyperthermia. For agitation and hallucinations, the patient was treated with titrated IV lorazepam (2-4 mg q5-10min PRN) or intramuscular (IM) midazolam (5-10 mg), while antipsychotics were avoided due to seizure risk. Persistent myoclonus was managed with additional IV diazepam (5-10 mg).

The rhabdomyolysis protocol included continued IV fluids (NS/LR at 200-500 mL/hr) and sodium bicarbonate infusion (targeting urine pH 7.5-8.0) for CK >5,000 U/L. Electrolytes were monitored closely, with calcium gluconate and insulin/D5W prepared for potential hyperkalemia. Hypoglycemia (3.96 mmol/L) was corrected with 25g IV dextrose, followed by frequent glucose monitoring. Continuous cardiac monitoring was maintained, with serial assessments of CK, electrolytes, renal function, and arterial blood gases (ABGs). An expanded toxicology screen was sent, recognizing that standard tests may not detect ketamine.

Given the severity of presentation (persistent hyperthermia, CK >5,000, and airway concerns), the patient was transferred to the ICU for ongoing management. A psychiatry consultation was requested for substance use evaluation once stabilized. The patient’s contrast CT showing bladder/ureteric wall thickening and hydroureteronephrosis prompted urology consultation for potential ketamine-induced cystopathy. While activated charcoal (1g/kg, max 50g) was considered for possible PCP co-ingestion, it was withheld due to the protected airway requirement and presentation timing.

This case highlights the severe complications associated with suspected ketamine toxicity, with clinical features including altered mental status, hyperthermia, airway compromise, rhabdomyolysis, and autonomic instability. Ketamine, though widely used for procedural sedation and rapid sequence intubation (RSI), has a complex pharmacological profile that necessitates vigilant monitoring, especially in toxicological contexts.

In this case, the most significant complication was laryngospasm, a rare but life-threatening adverse reaction to ketamine, which necessitated RSI due to signs of airway obstruction. This finding is similar to the case reported by Burnett et al.[8] In which ketamine-associated laryngospasm and hypoxia occurred in a prehospital setting. In both cases, endotracheal intubation was required following episodes of laryngospasm after ketamine administration. In the present case, intravenous lidocaine was used pre-intubation to blunt airway reflexes, and neuromuscular blockade was cautiously achieved using succinylcholine or rocuronium due to the risk of hyperkalemia associated with rhabdomyolysis.

Green et al.[9] Conducted a meta-analysis of over 8,000 ketamine sedations and found no reliable predictors of laryngospasm, concluding that the complication is idiosyncratic and unpredictable, emphasizing the need for preparedness in all ketamine-sedated patients. This patient displayed severe agitation, hallucinations, and persistent myoclonus, managed with titrated benzodiazepines (IV lorazepam and IM midazolam). Notably, antipsychotics were avoided due to seizure risk.

The most common treatment-related issues were agitation and hallucinations, which were managed using titrated IV lorazepam (2–4 mg every 5–10 minutes as needed) or IM midazolam (5–10 mg), while antipsychotics were avoided due to the risk of seizures. Persistent myoclonus was also observed and treated with additional IV diazepam (5–10 mg), similar to the case reported by Kim et al., in which a pediatric patient without prior risk factors experienced a rare ketamine-induced generalized tonic-clonic seizure, highlighting the need for caution even in low-risk individuals due to ketamine’s dual proconvulsant and anticonvulsant potential.

In this case, IV benzodiazepines were the preferred agents for cardiovascular stabilization, primarily to manage ketamine-induced hypertension and tachycardia. This approach aligns with the findings of Dewhirst et al.[11] who compared ketamine and etomidate in RSI and emphasized ketamine’s generally favorable cardiovascular profile. However, they also noted that in conditions of catecholamine depletion, such as prolonged shock or severe intoxication, ketamine might paradoxically cause hypotension and even cardiac arrest. In our case, the patient tolerated ketamine-based RSI without experiencing hemodynamic collapse, possibly due to preserved catecholamine reserves, consistent with the observations of Dewhirst et al.[11]

In this case, the patient presented with critical hyperthermia (103°F), which was managed aggressively using both external and internal cooling methods, targeting a core temperature reduction to below 38.5°C within 30–60 minutes. Ice packs were applied to the neck, axilla, and groin, alongside the use of cooling blankets, evaporative cooling, and administration of cold IV fluids (4°C normal saline, 500–1000 mL). Although dantrolene was kept on standby for potential malignant hyperthermia, it was not ultimately administered. The associated rhabdomyolysis was managed with aggressive intravenous fluid resuscitation, aiming for a urine output of 1–2 mL/kg/hr, and urine alkalinization with sodium bicarbonate infusion was initiated when CK levels exceeded 5,000 U/L. Electrolyte imbalances, including hyperkalemia, were anticipated and proactively addressed using calcium gluconate and insulin with dextrose (D5W). The management approach aligns with that described by Larach MG et al.[12] In their report on malignant hyperthermia protocols.

In this case, hypoglycemia (3.96 mmol/L) was promptly corrected with 25g intravenous dextrose, followed by frequent glucose monitoring like the approach described by Shahani et al.[13] who reported on ketamine-associated complications. Continuous cardiac monitoring was maintained, along with serial assessments of CK, electrolytes, renal function, and ABGs. A comprehensive toxicology screen was sent, acknowledging that standard panels may fail to detect ketamine. In alignment with Shahani et al.’s findings, CT imaging in this patient revealed bladder wall thickening and hydroureteronephrosis, raising suspicion for ketamine-induced cystopathy. A urology consultation was obtained in response. While chronic urinary tract complications are increasingly documented among habitual ketamine users, such acute urinary changes are less frequently reported in the clinical setting.[13]

Due to the severity of symptoms, including persistent hyperthermia, rhabdomyolysis, and airway compromise, the patient was transferred to the ICU for ongoing supportive care. A psychiatric evaluation was arranged post-stabilization to assess for underlying substance use disorders. Although activated charcoal is sometimes indicated for co-ingestion with PCP-like agents, it was withheld here due to the need for airway protection and the timing of presentation.

This case describes a 24-year-old male who presented with altered mental status, agitation, hallucinations, hyperthermia, and signs of upper airway obstruction following suspected recreational drug use. Clinical findings, including hypoglycemia, dilated pupils, nystagmus, rhabdomyolysis, and elevated creatine kinase, suggested ketamine toxicity as the primary diagnosis, despite a mildly elevated PCP level. Rapid-sequence intubation was required due to intermittent laryngospasm and impending airway compromise.

Comprehensive management included IV benzodiazepines for agitation and cardiovascular stabilization, aggressive IV fluid resuscitation to treat rhabdomyolysis, and a multimodal cooling approach to address hyperthermia. Sodium bicarbonate therapy was initiated for elevated CK, and potential hyperkalemia was anticipated with calcium gluconate and insulin/D5W. Hypoglycemia was corrected with IV dextrose. Continuous monitoring of electrolytes, renal function, and cardiac status was maintained.

Imaging findings of bladder and ureteric wall thickening raised concerns for ketamine-induced cystopathy, prompting urology consultation. The patient was transferred to the ICU due to the severity of symptoms and complications. Activated charcoal was withheld, given the protected airway, and delayed presentation. This case underscores the importance of early recognition and aggressive, supportive management of ketamine toxicity, particularly when airway compromise, rhabdomyolysis, and hyperthermia are present, and highlights the need for toxicology screening and psychiatric evaluation in suspected substance abuse cases.

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Corresponding Author:
Sonam Shashikala BV
Independent Researcher, Department of Content
medtigo India Pvt Ltd, Pune, India
Email: venkateshsonams@gmail.com

Co-Authors:
Rabia Akram, Raziya Begum Sheikh, Mansi Srivastava, Shubham Ravindra Sali
Independent Researcher, Department of Content
medtigo India Pvt Ltd, Pune, India

Samatha Ampeti
Department of Pharmacology
Kakatiya University, University College of Pharmaceutical Sciences, Warangal, TS, India

All patient-related data were collected by Rabia Akram. The initial draft of this case report/review was compiled by Sonam Shashikala BV. The final review and editing were completed by Samatha Ampeti. All authors reviewed and approved the final version of the manuscript.

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This case report is based on a clinical case published in the “Cases” section of medtigo.com. The authors declare no conflicts of interest related to this publication.

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https://doi.org/10.63096/medtigo3084222

Sonam SBV, Rabia A, Samatha A, Raziya BS, Mansi S, Shubham RS. Neuropsychiatric and Autonomic Manifestations of Ketamine Toxicity in a 24-Year-Old Male. medtigo J Neurol Psychiatr. 2025;2(2):e3084222. doi:10.63096/medtigo3084222 Crossref